November 09, 2016
Testing a drug that starves cancer cells to death
BY Scott Merville
The first clinical study of a new drug designed to kill cancer cells by depriving them of the nutrients they need to survive is underway at MD Anderson. Named after MD Anderson’s Institute for Applied Cancer Science (IACS) where it was developed, IACS-10759 blocks the conversion of nutrients into the energy that fuels cancer cells.The study will enroll up to 48 patients with acute myeloid leukemia (AML) and is supported by a $3.5 million investment from The Leukemia & Lymphoma Society’s (LLS) Therapy Acceleration Program®.
All cells use two processes to make the energy they need to survive: oxidative phosphorylation (OXPHOS) and glycolysis. OXPHOS is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to feed cells. This usually takes place inside mitochondria, organelles inside cells that power the cells. Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolsim.
IACS-10759 interferes with the mitochondria that power the cells, and this inhibits OXPHOS. Normal cells can get around OXPHOS inhibition by turning up glycolysis; however, the IACS team led by Emilia di Francesco, Ph.D., associate director of Medicinal Chemistry, and Joe Marszalek, Ph.D., head of Translational Biology, identified a highly potent and specific OXPHOS inhibitor to target cancer cells that are unable to compensate in that way, and survive.
“The IACS model emphasizes the need for us to deeply understand the biological effects of drugs,” said Giulio Draetta, M.D., Ph.D., head of Therapeutics Discovery at MD Anderson.
To further this understanding, Marszalek and Di Francesco, collaborated with Marina Konopleva, M.D., Ph.D., professor of Leukemia, who could provide clinical expertise and models for studying AML.
The team has since identified subgroups in other blood cancers and a variety of solid-tumor cancers that could also be vulnerable to OXPHOS inhibition.
“We’re already working closely with several MD Anderson Cancer Moon Shots Program teams to develop IACS-10759 treatment for patients whose tumors rely on oxidative phosphorylation,” said IACS Executive Director Philip Jones, Ph.D.
Read more about this study in MD Anderson’s Newsroom.